DNA topoisomerase 2-alpha (TOP2A) (TOP2A)

DNA topoisomerase 2-alpha (TOP2A) is a critical nuclear enzyme responsible for altering DNA topology by generating transient double-strand breaks, which facilitates the passage of one DNA helix through another. This activity is indispensable for fundamental cellular processes including DNA replication, transcription, and the segregation of daughter chromosomes during mitosis (UniProt P11388). TOP2A is frequently overexpressed in rapidly proliferating cancer cells, correlating with tumor grade and aggressiveness (PubMed: 21575011). Therapeutic agents known as topoisomerase II poisons, such as etoposide and doxorubicin, specifically target the DNA–TOP2A cleavage complex by stabilizing the covalent intermediate. This prevents the enzyme from re-ligating the DNA strands, leading to an accumulation of permanent double-strand breaks that ultimately trigger programmed cell death (PubMed: 19301235). Despite their clinical efficacy, these drugs are associated with significant risks, including dose-limiting cardiotoxicity and the potential for secondary leukemias resulting from genomic instability (PubMed: 25135934).

Other names

Topoisomerase II alphaTOP2DNA topoisomerase II alphaTOP-2TOP2A-DNA cleavage complex

Topoisomerase II poison; stabilizes the covalent DNA–TOP2A cleavage complex to prevent DNA re-ligation, inducing double-strand breaks and apoptosis.